New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients.

Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice.

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group's exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear.

Multicentric Standardization of Protocols for the Diagnosis of Human Mitochondrial Respiratory Chain Defects.

The quantification of mitochondrial respiratory chain (MRC) enzymatic activities is essential for diagnosis of a wide range of mitochondrial diseases, ranging from inherited defects to secondary dysfunctions. MRC lesion is frequently linked to extended cell damage through the generation of proton leak or oxidative stress, threatening organ viability and patient health. However, the intrinsic challenge of a methodological setup and the high variability in measuring MRC enzymatic activities represents a major obstacle for comparative analysis amongst institutions.

Secondary CoQ deficiency, bioenergetics unbalance in disease and aging.

Coenzyme Q (CoQ ) deficiency is a rare disease characterized by a decreased accumulation of CoQ in cell membranes. Considering that CoQ synthesis and most of its functions are carried out in mitochondria, CoQ deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ supplementation.

Na controls hypoxic signalling by the mitochondrial respiratory chain.

All metazoans depend on the consumption of O by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O to produce reactive oxygen species that can drive cell adaptations, a phenomenon that occurs in hypoxia and whose precise mechanism remains unknown. Ca is the best known ion that acts as a second messenger, yet the role ascribed to Na is to serve as a mere mediator of membrane potential.

Comparative Bioavailability of Different Coenzyme Q10 Formulations in Healthy Elderly Individuals.

Coenzyme Q10 (CoQ10) plays a central role in mitochondrial oxidative phosphorylation. Several studies have shown the beneficial effects of dietary CoQ10 supplementation, particularly in relation to cardiovascular health. CoQ10 biosynthesis decreases in the elderly, and consequently, the beneficial effects of dietary supplementation in this population are of greater significance.

Design of High-Throughput Screening of Natural Extracts to Identify Molecules Bypassing Primary Coenzyme Q Deficiency in .

Coenzyme Q (CoQ) deficiency syndrome is a rare disease included in the family of mitochondrial diseases, which is a heterogeneous group of genetic disorders characterized by defective energy production. CoQ biosynthesis in humans requires at least 11 gene products acting in a multiprotein complex within mitochondria. The high-throughput screening (HTS) method based on the stabilization of the CoQ biosynthesis complex (Q-synthome) produced by the gene overexpression is proven here to be a successful method for identifying new molecules from natural extracts that are able to bypass the CoQ deficiency in yeast mutant cells.

Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.

Fatty acids and glucose are the main bioenergetic substrates in mammals. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of , a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle.

Biochemical Assessment of Coenzyme Q Deficiency.

Coenzyme Q (CoQ) deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ biosynthesis. Mutations in any of these genes are responsible for the primary CoQ deficiency, but there are also different conditions that induce secondary CoQ deficiency including mitochondrial DNA (mtDNA) depletion and mutations in genes involved in the fatty acid β-oxidation pathway.

Secondary coenzyme Q10 deficiencies in oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders.

We evaluated the coenzyme Q₁₀ (CoQ) levels in patients who were diagnosed with mitochondrial oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders (n=72). Data from the 72 cases in this study revealed that 44.4% of patients showed low CoQ concentrations in either their skeletal muscle or skin fibroblasts.

Mitochondrial responsibility in ageing process: innocent, suspect or guilty.

Ageing is accompanied by the accumulation of damaged molecules in cells due to the injury produced by external and internal stressors. Among them, reactive oxygen species produced by cell metabolism, inflammation or other enzymatic processes are considered key factors. However, later research has demonstrated that a general mitochondrial dysfunction affecting electron transport chain activity, mitochondrial biogenesis and turnover, apoptosis, etc.

Factors Influencing the Contents of Coenzyme Q10 and Q9 in Olive Oils.

The health effects of olive oil are attributed to its high content of oleic acid and other constituents, particularly its phenolic fraction. Olive oil also contains other substances with potential health effects such as coenzyme Q10 (CoQ10) and coenzyme Q9 (CoQ9). The objective of our study was to investigate some factors that could influence the quantity of coenzyme Q (CoQ) in olive oils.

Is coenzyme Q a key factor in aging?

Coenzyme Q (Q) is a key component for bioenergetics and antioxidant protection in the cell. During the last years, research on diseases linked to Q-deficiency has highlighted the essential role of this lipid in cell physiology. Q levels are also affected during aging and neurodegenerative diseases.

Coenzyme Q supports distinct developmental processes in Caenorhabditis elegans.

Coenzyme Q (Q) regulates aging in Caenorhabditis elegans, and its deficiency leads to a variety of pathologies in humans. We used a coq-8 deleted strain to study the role of Q in C. elegans development and how it influences life span.

C. elegans knockouts in ubiquinone biosynthesis genes result in different phenotypes during larval development.

Ubiquinone is an essential molecule in aerobic organisms to achieve both, ATP synthesis and antioxidant defence. Mutants in genes responsible of ubiquinone biosynthesis lead to non-respiring petite yeast. In C.

Coenzyme Q is irreplaceable by demethoxy-coenzyme Q in plasma membrane of Caenorhabditis elegans.

A procedure was developed to isolate fractions enriched in plasma membrane from Caenorhabditis elegans. Coenzyme Q9 (Q9) was found in plasma membrane isolated from either wild-type or long-lived qm30 and qm51 clk-1 mutant strains of Caenorhabditis elegans, along with dietary coenzyme Q8 (Q8) and the biosynthetic intermediate demethoxy-Q9 (DMQ9). NADH was able to reduce both Q8 and Q9, but not DMQ9.

Differential expression pattern of coq-8 gene during development in Caenorhabditis elegans.

Coenzyme Q (Q) and the genes involved in its biosynthesis are involved in aging and development of Caenorhabditis elegans. Q is synthesized by at least eight highly conserved nuclear coq genes, but this biosynthesis pathway and its regulation is not known. The coq-8 gene sequence has homology to the ABC-1 family kinases and is the only known candidate for a possible regulation of this pathway.

The role of ubiquinone in Caenorhabditis elegans longevity.

Aging is an irreversible physiological process that affects all living organisms. Different mutations in the insulin signaling pathway and caloric restriction have been shown to retard aging in Caenorhabditis elegans. In addition, mutations or RNAi silencing of components of the respiratory chain results in the modification of adult life span.

Caenorhabditis elegans ubiquinone biosynthesis genes.

Ubiquinone (coenzyme Q, Q) is an essential lipid electron carrier in the mitochondria respiratory chain, and also functions as antioxidant and participates as a cofactor of mitochondrial uncoupling proteins. Caernorhabditis elegans synthesize Q9, but both dietary Q8 intake and endogenous Q9 biosynthesis determine Q balance. Thus, it is of current interest to know the regulatory mechanisms of Q9 biosynthesis in this nematode.

Silencing of ubiquinone biosynthesis genes extends life span in Caenorhabditis elegans.

Ubiquinone (coenzyme Q; Q) is a key factor in the mitochondria electron transport chain, but it also functions as an antioxidant and as a cofactor of mitochondrial uncoupling proteins. Furthermore, Q isoforms balance in Caenorhabditis elegans is determined by both dietary intake and endogenous biosynthesis. In the absence of synthesis, withdrawal of dietary Q8 in adulthood extends life span.

A novel plasma membrane quinone reductase and NAD(P)H:quinone oxidoreductase 1 are upregulated by serum withdrawal in human promyelocytic HL-60 cells.

We have studied changes in plasma membrane NAD(P)H:quinone oxidoreductases of HL-60 cells under serum withdrawal conditions, as a model to analyze cell responses to oxidative stress. Highly enriched plasma membrane fractions were obtained from cell homogenates. A major part of NADH-quinone oxidoreductase in the plasma membrane was insensitive to micromolar concentrations of dicumarol, a specific inhibitor of the NAD(P)H:quinone oxidoreductase 1 (NQOI, DT-diaphorase), and only a minor portion was characterized as DT-diaphorase.